On September 21, the U.S. Food and Drug Administration (FDA) granted regular approval to selpercatinib (Retevmo) for adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with a RET gene fusion (as detected by an FDA-approved test).
The FDA also approved the Oncomine Dx Target (ODxT) Test (Thermo Fisher Scientific) as a companion diagnostic for selpercatinib.
Selpercatinib was previously granted accelerated approval for the NSCLC indication on May 8, 2020, based on initial overall response rate and duration of response in 144 patients enrolled in the LIBRETTO-001 trial (ClinicalTrials.gov identifier: NCT03157128), a multicenter, open-label, multicohort trial. The conversion to regular approval was based on data from an additional 172 patients and 18 months of additional follow-up to assess durability of response.
Efficacy was demonstrated in total of 316 patients with locally advanced or metastatic RET fusion–positive NSCLC. Patients received selpercatinib until disease progression or unacceptable toxicity.
The primary efficacy measures were overall response rate and duration of response as determined by a blinded independent review committee. Among 69 treatment-naive patients, the overall response rate was 84% (95% confidence interval [CI] = 73%–92%) with a duration of response of 20.2 months (95% CI = 13–not estimable). Among 247 patients previously treated with platinum-based chemotherapy, the overall response rate was 61% (95% CI = 55%–67%) with a duration of response of 28.6 months (95% CI = 20–not estimable).
The median age of patients was 61 years (range = 23–92). Selected demographics were as follows: 58% female; 49% White, 41% Asian, and 5% Black; 97% had an Eastern Cooperative Oncology Group performance status 0 or 1; and 97% had metastatic disease. Previously treated patients received a median of two prior systemic therapies (range = 1–15); 58% had received prior anti–PD-1/PD-L1 therapy.
The most common adverse reactions (≥ 25%) in patients were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.
The recommended selpercatinib dose based on body weight is:
This application was granted Breakthrough designation and Orphan Drug designation.